A variety of systems have been described to enhance the transdermal flux of various bioactive molecules across the skin barrier. Compositions have been described containing chemical penetration enhancers from such diverse groups as alkanes, alkenes, amides, amines, amine oxides, carboxylic acids, esters, ethers, halocarbons, ketones, and sulfoxides.
Chemical penetration compositions have also been described that, for one purpose or another, involve the use of either lower or higher alcohols, or occasionally both lower and higher alcohols. See, e.g., U.S. Pat. Nos. 4,593,048 (Sato et al.), 4,615,699 (Gale et al.), 4,645,502 (Gale et al.), and 4,752,612 (Saito et al.), GB Patent Application Nos. 2,075,837 (Noda et al.), GB Patent Application No. 2,098,865 (Franz) and 2,194,147 (Sato et al.), Japanese application Kokai No. JP63-35521 (Ohtsuka et al.), and European Patent Application Publication Nos. 043,738 (Wickett et al.), 127,468 (Yamada et al.), 255,485 (Mahjour et al.), 267,617 (Patel et al.), and 271,983 (Francoeur et al.), as well as Sugibayashi et al., Chem. Pharm. Bull., 36(4):1519-1528 (1988).
Exemplary compositions involving the use of both lower and higher alcohols in an aqueous system include U.S. Pat. No. 4,006,218 (Sipos). The '218 patent describes topical compositions that include, inter alia, a potentiator that is used at a range described as between at least 0.05% (by weight) and about 15 to 18%, and preferably from about 1% to about 12% by weight of the composition. Suitable potentiators include, for instance, the alcohols described in Group I therein.
Example 6 of the '218 patent describes topical compositions containing, inter alia, ethanol at a concentration of 50% by weight, as well as various potentiators, each at a concentration of 10%. As can be seen by the results in TABLE III of the '218 patent, the potentiators coming within the definition of Group I of that patent (i.e., pentanol, hexanol, heptanol, and 2-heptanol) fared poorly compared to other potentiators. It can be determined in retrospect that for each Group I potentiator used, its concentration (i.e., 10%) was below the concentration that would saturate the respective composition. This is either because the saturating concentration was higher than the concentration actually used for a particular potentiator, or because the particular potentiator was infinitely miscible in the particular system, and therefore would have no saturating concentration.
U.K. Patent No. GB 2 128 087B (Asche et al.) describes topically administrable anti-inflammatory pharmaceutical compositions containing, together with other required ingredients, from 10 to 50% by weight of a water-soluble, volatile lower alkanol having from 2 up to and including 4 carbon atoms, and a lipid component that can include saturated or unsaturated fatty alcohols having, for example, 1 or 2 hydroxy functions and a carbon atom number of approximately from 6 to 34.
Japanese Kokai No. J62-230710 (Hori, et al.) describes the use of a number of penetration enhancement agents for use in a hair tonic with the hair growth compound minoxidil. The agents described include C.sub.7 to C.sub.15 alcohols, used at between 0.01 and 20% by weight of minoxidil. The exemplified formulation also contains ethanol at a concentration of 44.5% by weight.
No reference appears to use both an aqueous solution of lower alcohol together with higher alcohol used at a substantially saturated level, nor therefore do the references teach or suggest the advantages to be gained by the use of such a composition.